Journal of Clinical Oncology, Vol 24, No 27 (September 20), 2006: pp. 4499-4506
© 2006 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2006.06.5037
Less Toxicity by Optimizing Chemotherapy, but Not by Addition of Granulocyte Colony-Stimulating Factor in Children and Adolescents With Acute Myeloid Leukemia: Results of AML-BFM 98
Ursula Creutzig,
Martin Zimmermann,
Thomas Lehrnbecher,
Norbert Graf,
Johann Hermann,
Charlotte M. Niemeyer,
Alfred Reiter,
Jörg Ritter,
Michael Dworzak,
Jan Stary,
Dirk Reinhardt
From the Department of Hematology/Oncology, University Children's Hospital, Muenster; Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover; Department of Pediatric Hematology and Oncology, University of Frankfurt, Frankfurt; Department of Pediatric Hematology and Oncology, University Children's Hospital, Homburg; Department of Pediatric Hematology and Oncology, University Children's Hospital, Jena; Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg; Department of Pediatric Hematology and Oncology, University Children's Hospital, Giessen, Germany; St Anna Children's Hospital and Children's Cancer Research Institute, Vienna, Austria; and the Department of Pediatric Hematology/Oncology, University Hospital Motol, Prague, Czech Republic
Address reprint requests to Ursula Creutzig, MD, PhD, Universitätsklinikum Münster, Klinik und Poliklinik für Kinderund Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Albert-Schweitzer-Str 33, D-48129 Münster, Germany; e-mail: ursula{at}creutzig.de
PURPOSE: To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone).
PATIENTS AND METHODS: Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy.
RESULTS: Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%).
CONCLUSION: Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.
Supported by the Deutsche Krebshilfe e.V.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike Complore Connotea Del.icio.us Digg Facebook Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
B. V. Balgobind, S. C. Raimondi, J. Harbott, M. Zimmermann, T. A. Alonzo, A. Auvrignon, H. B. Beverloo, M. Chang, U. Creutzig, M. N. Dworzak, et al.
Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study
Blood,
September 17, 2009;
114(12):
2489 - 2496.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Tsukimoto, A. Tawa, K. Horibe, K. Tabuchi, H. Kigasawa, M. Tsuchida, H. Yabe, H. Nakayama, K. Kudo, R. Kobayashi, et al.
Risk-Stratified Therapy and the Intensive Use of Cytarabine Improves the Outcome in Childhood Acute Myeloid Leukemia: The AML99 Trial From the Japanese Childhood AML Cooperative Study Group
J. Clin. Oncol.,
August 20, 2009;
27(24):
4007 - 4013.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. T. Horan, T. A. Alonzo, G. H. Lyman, R. B. Gerbing, B. J. Lange, Y. Ravindranath, D. Becton, F. O. Smith, and W. G. Woods
Impact of Disease Risk on Efficacy of Matched Related Bone Marrow Transplantation for Pediatric Acute Myeloid Leukemia: The Children's Oncology Group
J. Clin. Oncol.,
December 10, 2008;
26(35):
5797 - 5801.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Messerer, J. Engel, J. Hasford, M. Schaich, G. Ehninger, C. Sauerland, T. Buchner, A. Schumacher, R. Krahl, D. Niederwieser, et al.
Impact of different post-remission strategies on quality of life in patients with acute myeloid leukemia
Haematologica,
June 1, 2008;
93(6):
826 - 833.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. H. Meyer, M. Queudeville, S. M. Eckhoff, U. Creutzig, D. Reinhardt, L. Karawajew, W.-D. Ludwig, K. Stahnke, and K.-M. Debatin
Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML
Blood,
March 1, 2008;
111(5):
2899 - 2903.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. J. Lange, F. O. Smith, J. Feusner, D. R. Barnard, P. Dinndorf, S. Feig, N. A. Heerema, C. Arndt, R. J. Arceci, N. Seibel, et al.
Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group
Blood,
February 1, 2008;
111(3):
1044 - 1053.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. J.L. Kaspers and C. M. Zwaan
Pediatric acute myeloid leukemia: towards high-quality cure of all patients
Haematologica,
November 1, 2007;
92(11):
1519 - 1532.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Sung, P. C. Nathan, S. M.H. Alibhai, G. A. Tomlinson, and J. Beyene
Meta-analysis: Effect of Prophylactic Hematopoietic Colony-Stimulating Factors on Mortality and Outcomes of Infection
Ann Intern Med,
September 18, 2007;
147(6):
400 - 411.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Lehrnbecher, M. Zimmermann, D. Reinhardt, M. Dworzak, J. Stary, and U. Creutzig
Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia
Blood,
February 1, 2007;
109(3):
936 - 943.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|